Women's Reproductive Traits Schizophrenia Risk

A groundbreaking study published in BMC Psychiatry by Wenxi Sun, Xiaohui Wu, Haidong Yang, Shiting Yuan, Jun Chen, Yiru Fang, and Xiaobin Zhang has unveiled a potential causal relationship between women's reproductive traits and the risk of developing schizophrenia (SCZ). Utilizing a sophisticated method known as Mendelian randomization (MR), the researchers aimed to clarify if certain reproductive traits in women could influence the likelihood of SCZ, a question that has intrigued scientists but remained unanswered until now.

#### The Study at a Glance

The study meticulously analyzed data from extensive genome-wide association studies (GWAS) that included individuals of European ancestry, ranging from 176,881 to 418,758 participants. The focus was on five female reproductive variables, with summary-level information on SCZ drawn from a GWAS meta-analysis involving 320,404 people. The approach was twofold: initially, a univariable MR (UVMR) study was conducted, followed by a multivariable MR (MVMR) study to validate the findings thoroughly.

#### Key Findings

One of the most striking outcomes of this research was the significant association discovered between the age at first sexual intercourse (AFS) and the risk of SCZ. Specifically, the study found that a genetically predicted later AFS was linked to a reduced risk of SCZ, with an odds ratio (OR) of 0.632, indicating a strong protective effect against SCZ.

To ensure the reliability of these results, the researchers employed various sensitivity analyses, including MR-Egger, weighted median, and mode regression methods, all of which supported the initial findings. Furthermore, the study went a step further by adjusting for other factors such as body mass index, years of schooling, and smoking initiation through MVMR, which still demonstrated a significant causal effect of AFS on SCZ risk.

#### Implications and Conclusion

The implications of this study are profound, suggesting that early AFS could be a risk factor for developing SCZ. This insight opens new avenues for schizophrenia research and prevention, emphasizing the importance of reproductive healthcare awareness among women as a potential strategy to reduce SCZ risk.

By shedding light on the complex interplay between reproductive traits and mental health, this study not only contributes to our understanding of schizophrenia's etiology but also highlights the need for a holistic approach to women's health that considers the broad implications of reproductive experiences on overall well-being.

This pioneering research underscores the power of genetic studies in uncovering the underlying causes of mental health conditions, paving the way for more targeted interventions and informed healthcare strategies to mitigate the risk of schizophrenia and improve the lives of women worldwide.

Wenxi Sun, Xiaohui Wu, Haidong Yang, Shiting Yuan, Jun Chen, Yiru Fang & Xiaobin Zhang

BMC Psychiatry volume 24, Article number: 161 (2024)

New Predictor for COVID-19 Severity

### Unveiling a New Predictor for COVID-19 Severity Through Antibody Research

In a pioneering study conducted by Drexel University's College of Medicine, researchers have made a significant discovery that could potentially forecast the severity of COVID-19 in patients. Their findings, recently published in the journal *Nature Communications*, revolve around the analysis of immunoglobulin M (IgM) antibodies, specifically the sugar structures, known as glycans, attached to them. This research underscores the critical role that our immune system's response plays in combating the SARS-CoV-2 virus and the ensuing illness.

Traditionally, the focus has been on long-lasting immunoglobulin G (IgG) antibodies when studying the body's defense against infections. However, this study shifts the spotlight to IgM antibodies, which appear earlier in the immune response. IgM's role is pivotal in how our bodies detect and fight off pathogens like bacteria and viruses. The Drexel research team, intrigued by the lack of attention towards IgM glycans, decided to delve into how these sugar modifications affect the antibody's function and, consequently, the disease's severity.

The study observed changes in IgM glycan structures in hospitalized COVID-19 patients and linked these alterations to the severity of the infection. These glycan changes seem to influence the antibody's effectiveness in battling the infection. The researchers propose that the immune system modifies IgM glycans, especially during severe cases of the disease, which may trigger an overactive immune response potentially leading to complications like organ failure.

This insight into IgM glycans and their impact on COVID-19 severity is groundbreaking. While there isn't a rapid test available yet for analyzing these glycans in patients, the findings pave the way for a deeper understanding of the immune response to COVID-19. It opens up possibilities for early identification of patients who might be at risk of severe disease, thus helping in tailoring more effective management strategies.

Moreover, this discovery has profound implications for the development of immunotherapies. Understanding the glycosylation of antibodies allows for glycoengineering – a process where antibodies are fine-tuned to enhance their pathogen-killing capabilities while minimizing inflammatory responses. This could be instrumental in designing treatments that are both effective in fighting the virus and safe for the patient.

The study, which began with a cohort of 22 patients, emphasizes the need for larger-scale research to validate these findings and explore their application in predicting long-COVID symptoms. This research not only exemplifies the importance of interdisciplinary collaboration but also highlights the crucial role of patient participation in advancing scientific knowledge.

As we continue to navigate the challenges posed by COVID-19, discoveries like these offer hope for more precise and personalized healthcare interventions, potentially transforming our approach to managing and treating this unpredictable disease.

Researchers find possible predictor of COVID-19 severity | MDLinx

A New Approach to Predicting Diabetes Risk

In recent research from Edith Cowan University (ECU), a groundbreaking discovery suggests that a simple blood test could significantly enhance our ability to predict an individual's risk of developing type 2 diabetes. This new study focuses on the combined analysis of inflammatory biomarkers, which shows promise in early identification and possibly preventing the onset of this chronic condition.

Traditionally, doctors have relied on measuring levels of high-sensitivity C-reactive protein (CRP) to gauge inflammation and predict diabetes risk. However, this latest research advocates for the joint assessment of CRP and another biomarker known as the monocyte to high-density lipoprotein ratio (MHR). By evaluating these markers together, scientists believe they can improve the accuracy of diabetes risk prediction and better understand the complications that may arise with the disease.

Over a span of nearly ten years, the study monitored more than 40,800 participants who did not have diabetes at the start. Out of these, over 4,800 individuals developed type 2 diabetes. The findings revealed a significant interaction between the MHR and CRP levels, indicating that individuals with rising levels of both biomarkers had a substantially higher risk of developing diabetes.

This association between chronic inflammation (as indicated by the combined levels of MHR and CRP) and the risk of diabetes appeared to be influenced by various factors including age, sex, hypertension, high cholesterol, or prediabetes. Notably, the risk was found to be more pronounced in females, possibly due to differences in sex hormones.

The implications of this study are far-reaching. It highlights chronic inflammation's role in the onset of early diabetes, particularly in light of the global rise in cases among young adults, especially in developing countries. By leveraging the relationship between inflammation and diabetes, healthcare providers can identify individuals at risk earlier and tailor interventions more effectively.

Moreover, the study underscores the importance of lifestyle factors in managing inflammation and, by extension, diabetes risk. Diet, sleep, stress, and metabolic regulation all play crucial roles in influencing inflammation levels. The researchers advocate for the inclusion of MHR and CRP measurements in clinical settings, citing their cost-effectiveness and widespread availability as tools for early diabetes risk prediction.

This research not only opens new avenues for diabetes prevention but also emphasizes the critical need for personalized healthcare approaches. By identifying at-risk individuals early, we can implement lifestyle changes and interventions that may delay or prevent the onset of type 2 diabetes, ultimately reducing the burden of this disease on individuals and healthcare systems worldwide.

Blood test could determine diabetes risks | MDLinx

the Link Between Early Hypertension and Stroke

### Understanding the Link Between Early Hypertension and Stroke Risk in Black Women

Recent research highlights a concerning trend: Black women who develop high blood pressure before the age of 35 are three times more likely to experience a stroke in midlife. This finding comes from the Black Women's Health Study, which has been tracking the health of 59,000 participants across the United States since the 1990s. Furthermore, those who develop hypertension before age 45 are at double the risk.

The study sheds light on a significant health concern: young Black women are facing strokes at an early age, which could lead to a lifetime of disability during what could be the most active periods of their lives. Despite advancements in reducing stroke rates among older populations, strokes in midlife are becoming more prevalent, especially among Black women who historically face higher rates of high blood pressure and strokes.

The research, presented by Dr. Hugo J. Aparicio, underlines the critical nature of hypertension as a risk factor for stroke, emphasizing that this is not just an issue for the elderly but for younger individuals as well, particularly Black women. The study suggests that monitoring blood pressure from an early age is crucial, alongside adopting lifestyle changes such as a healthy diet, regular physical activity, and managing other cardiovascular risk factors.

Additionally, the study points to psychosocial stressors, like financial strain, racism, and the burden of caregiving, as contributing factors to the increased risk of hypertension and stroke among Black women. This highlights the need for a holistic approach to healthcare that includes regular screenings for high blood pressure and other cardiovascular risk factors, as well as addressing the broader social and environmental factors that affect health.

This information underscores the importance of early intervention and comprehensive care strategies to mitigate the risk of stroke and improve the overall health outcomes for Black women.

By understanding these risks and taking proactive steps towards healthier lifestyles and regular healthcare screenings, we can help reduce the incidence of hypertension and stroke in this high-risk population, ensuring a healthier future for all.

Hypertension Before 35 Tied to Triple Stroke Risk in Midlife

Ginkgo Injections Tied to Cognitive Recovery

New Research: Ginkgo Biloba Extract Injection Effective in Restoring Cognitive Function after Stroke

February 7, 2024, Sue Hughes

A study has shown that a 14-day infusion of an ingredient extracted from Ginkgo biloba (Ginkgo biloba) is effective in improving cognitive function in the early recovery phase of stroke. The study was conducted in 100 centers in China on 3,452 patients with acute ischemic stroke. Patients enrolled within 48 hours of onset were randomized to receive either a daily infusion of 25 mg of ginkgo diterpene lactone meglumine (GDLM), a bioactive component of Ginkgo biloba, for 14 days or placebo The patients were randomly assigned to a group receiving an infusion of

When cognitive function was assessed by the Montreal Cognitive Assessment Score before treatment, after 14 days of treatment, and after 90 days of treatment, it was found that the group of patients who received Ginkgo biloba extract injections improved their scores by an average of 3.93 points after 14 days and 5.51 points after 90 days, compared with the placebo group The results of the study were as follows. Notable improvements were seen particularly in visuospatial, verbal, attention, and abstract thinking scores.

However, the follow-up period of this study was 90 days, and further research is needed to determine the long-term effects of GDLM injections. It is also believed to have a neuroprotective effect by improving hypoxic tolerance of cerebral cells, increasing cerebral blood flow, antioxidant, anti-inflammatory and anti-apoptotic (programmed cell death) effects. Laboratory studies also suggest that GDLM may promote the secretion of chemicals that prevent neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease.

Ginkgo biloba is an herb extracted from one of the oldest living trees native to East Asia and widely used in traditional Chinese medicine. Ginkgo biloba supplements are widely available in the United States, but are not approved as drugs.

If this new research proves effective in future clinical trials, it could be an important tool to help improve cognitive function in patients after ischemic stroke. However, it must demonstrate the same standards of efficacy and safety as all prescription drugs.

Ginkgo Injections Tied to Cognitive Recovery Post Stroke

統合失調症における抗うつ薬、ベンゾジアゼピンの使用および抗コリン薬負荷と認知能力との関連性

統合失調症の患者さんにおいて、日常生活に影響を及ぼす認知機能障害が見られます。この研究では、抗うつ薬、特にSNRI（セロトニン・ノルアドレナリン再取り込み阻害剤）が認知機能、特に反応時間の速さにどのような影響を及ぼすかを検討しました。また、ベンゾジアゼピン類や抗コリン作用を持つ薬剤が認知機能に与える影響についても調査しました。フィンランドで収集された大規模な患者コホート（n=10,410）から、統合失調症と診断された成人（n=3365）を対象に、薬剤使用状況と認知機能の関連を分析しました。認知機能は、特に反応時間と視覚学習の観点から評価されました。

研究の結果、一般的な抗うつ薬の使用は認知機能の評価結果、すなわち反応時間や視覚学習とは関連がないことが示されました。しかし、SNRIの使用は反応時間の速さと関連があることが見出されました。これはSNRIがある条件下で認知機能に肯定的な影響を与える可能性があることを示唆しています。一方で、ベンゾジアゼピン類や抗コリン作用が強い薬剤の使用は、認知機能の低下、特に反応時間の遅延や視覚学習の困難と関連していることが確認されました。これらの結果から、統合失調症の患者さんの治療において、抗うつ薬の選択やベンゾジアゼピン、抗コリン作用を持つ薬剤の使用には注意が必要であると結論付けられます。特に、ベンゾジアゼピンの使用を避け、薬剤の抗コリン作用による負担を考慮することが推奨されます。

Cognitive dysfunction affecting daily life is observed in patients with schizophrenia. In this study, we examined how antidepressants, particularly serotonin-noradrenaline reuptake inhibitors (SNRIs), affect cognitive function, particularly reaction time speed. The study also investigated the effects of benzodiazepines and drugs with anticholinergic properties on cognitive function. We analyzed the association between medication use and cognitive function in adults diagnosed with schizophrenia (n=3365) from a large patient cohort (n=10,410) collected in Finland. Cognitive function was assessed specifically in terms of reaction time and visual learning.
Study results showed that general antidepressant use was not associated with the assessed results of cognitive function, i.e., reaction time and visual learning. However, SNRI use was found to be associated with faster reaction times. This suggests that SNRIs may have a positive impact on cognitive function under certain conditions. On the other hand, use of benzodiazepines and other medications with strong anticholinergic effects were found to be associated with cognitive decline, particularly delayed reaction time and visual learning difficulties. Based on these results, it can be concluded that caution should be exercised in the choice of antidepressants and the use of benzodiazepines and anticholinergic agents in the treatment of patients with schizophrenia. In particular, it is recommended to avoid the use of benzodiazepines and to consider the burden caused by the anticholinergic effects of the drugs.

Mäkipelto V, Tuulio-Henriksson A, Hakulinen C, Niemelä S, Lähteenvuo M, Wegelius A, Kieseppä T, Isometsä E, Tiihonen J, Kampman O, Lahdensuo K, Mazumder A, Suvisaari J, Holm M.

Schizophr Res. 2024

個人用保護具と新型コロナウイルス感染症 (Covid-19)

コロナウイルス感染症2019（COVID-19）の脅威に対応し、医療現場における感染管理と予防策の適切な使用は非常に重要です。COVID-19は、重症急性呼吸器症候群コロナウイルス2（SARS-CoV-2）によって引き起こされます。感染経路には、直接接触（患者の呼吸飛沫やエアロゾルとの接触）と間接接触（汚染された表面や備品との接触）があります。

医療従事者がSARS-CoV-2感染を予防するための最善の方法は、個人防護具（PPE）の着脱に関する訓練を受け、能力を証明することです。米国疾病予防管理センター（CDC）および所属施設のガイドラインに従ってPPEを着脱する方法が異なります。

PPEには手袋、ガウン、N95以上のレスピレーター、フルフェイスシールドまたはゴーグルが含まれます。レスピレーターが利用できない場合は、フェイスマスクで代用することが可能です。使用するPPEは、耐液性のガウンやカバーオール、医療用手袋、NIOSH認定のN95レスピレーターまたはPAPR（動力式空気清浄呼吸器）などです。

PPEの着脱手順は以下の通りです：

1. PPEを着用する前に、十分な水分補給とトイレを済ませ、石鹸と水で手を洗います。
2. スクラブに着替え、長い髪を固定し、アクセサリーを外します。
3. ガウンを頭からかぶり、必要に応じて首の後ろで留めます。
4. N95レスピレーターを顔に近づけ、ストラップを固定し、鼻ストリップを調整します。
5. フェイスシールドを装着し、手袋をはめます。

PPEの除去手順は以下の通りです：

1. セカンドグローブテクニックを用いて手袋を取り外します。
2. ガウンを脱ぎ、廃棄します。
3. 病室を出たら、フェイスシールドを取り外し、廃棄または適切な容器に入れます。
4. N95レスピレーターを取り外し、廃棄またはリサイクルします。
5. それぞれのステップの後に手を消毒します。

PPEを正しく着用し、取り外し、廃棄することで、医療従事者と患者双方の保護が可能となります。

Rafael Ortega et a. NEJM. 2024.

プラセボはうつ病の神経可塑性を刺激する

この論文は、プラセボ効果が無作為化比較試験（RCT）や臨床介入で異なる結果をもたらすというパラドックスについて述べています。通常、プラセボは無効であると想定されますが、実際には多くの場合に効果を示します。特に、うつ病の治療においてプラセボ効果は顕著です。この論文では「神経可塑性プラセボ理論」という新しい考え方を提案しています。この理論によれば、プラセボ効果は、脳の特定の領域、特に前頭葉と辺縁系の神経可塑性、つまり脳の構造や機能が変化する能力に関連しています。

この理論は、抗うつ薬の臨床試験における神経放射線学的な証拠によって支持されています。脳の前頭葉-辺縁系の変化が観察され、これがプラセボ効果と関連していることが示唆されています。さらに、この理論が正しい場合、プラセボはうつ病だけでなく他の病態においても、部分的に有効な治療法として機能する可能性があります。このことは、臨床試験のデザインや、プラセボの臨床現場での使用において大きな影響をもたらすでしょう。

最後に、この論文はプラセボ効果とプラセボ反応という用語を「プラセボ治療」という一つの用語に統合することを提案しています。これは、前頭葉-辺縁系の神経可塑性が、プラセボを部分的に有効な治療として考える際の共通の要素であるためです。

Seymour J, Mathers N.

Front Psychiatry. 2024

うつ病に先行する便秘

本研究は、便秘がうつ病の発症に先行する可能性を探るもので、一般にうつ病の身体症状や抗うつ薬治療の副作用として考えられがちな便秘と、うつ病との関連を調べました。この研究では、腸脳軸仮説を基に、うつ病と便秘の関係が双方向である可能性を考慮しました。

研究方法として、UK Biobankのデータを用いた後ろ向きコホート研究を実施しました。2006年から2010年の間にうつ病を発症していない成人を対象とし、便秘の状態は電子カルテの診断コードやベースラインの質問票を用いて判定しました。共変量として、社会人口統計学的特性や生活様式因子、健康状態、常用薬などのデータも収集しました。うつ病の発症はベースラインから2022年までのデータを元に判定し、副次アウトカムとして抑うつ症状も調査しました。

結果として、449,459人の参加者のうち4.1％が便秘を経験し、同じく4.1％がうつ病を発症しました。便秘の経験はうつ病のリスクを2.28倍に高め、共変量を調整した後でも便秘のある人は便秘のない人に比べてうつ病の発症リスクが48％高いことが明らかになりました。自己報告による便秘と診断された便秘の両方が、うつ病の高リスクと関連していることも判明しました。

この研究から、便秘がうつ病の独立した危険因子または前駆症状である可能性が示唆されています。消化器内科医やプライマリケア医は、便秘患者の抑うつ症状に対して、より注意を払う必要があると結論付けられています。

Yun Q, Wang S, Chen S, Luo H, Li B, Yip P, Yu X, Yang Z, Sha F, Tang J.EClinicalMedicine. 2024

CARTaGENEプロジェクトにおける超加工食品の摂取、うつ病、糖尿病合併症のリスク

本研究は、2型糖尿病（T2D）の成人におけるうつ病、超加工食品（UPFs）の摂取、そして糖尿病特異的合併症の発症リスクとの関連性を評価することを目的としています。カナダ・ケベック州の40歳から69歳の成人を対象に行われた健康調査「CARTaGENE」のデータを基に、683人のT2D参加者を追跡調査しました。食事はカナダ式食事歴質問票に基づいて評価し、NOVA分類でUPFsの摂取量を分類。うつ病は、抑うつ症状の増加や抗うつ薬の使用で評価しました。

7年間の追跡で、105人が糖尿病関連合併症を発症しました。抑うつ症状が高く、UPFsの摂取量が多い参加者は、それらが少ない参加者に比べ、糖尿病合併症のリスクが最も高かったことが分かりました。特に、抑うつ症状が高く、抗うつ薬を使用している場合にUPFsの消費量が多いと、糖尿病合併症のリスクがさらに高まりました。

この研究結果から、うつ病とUPFsの大量摂取が併存する場合に糖尿病合併症のリスクが高まることが明らかになりました。したがって、糖尿病合併症の予防には、これらの危険因子の早期管理とモニタリングが重要であることが示唆されています。

Sen A, Brazeau AS, Deschênes S, Ramiro Melgar-Quiñonez H, Schmitz N.

Front Endocrinol (Lausanne). 2024